Phase separation in phosphatidylcholine bilayers as a predictor of inhibition of blood platelet aggregation by amantadines.

The ability of eleven amantadine derivatives to induce phase separation in dipalmitoyl phosphatidylcholine bilayers was studied by differential scanning calorimetry. The relative potency varied with the shape and size of the hydrocarbon cage. These agents also markedly inhibited blood platelet aggregation. The relative potencies of these compounds to induce phase separation showed a significant correlation (r = 0.70) with their platelet inhibitory activity suggesting that their pharmacologic action may be at the level of the platelet membrane. The effective concentration of the parent component amantadine is similar to its pharmacologic concentration suggesting its use as an anti-platelet drug.

Phase transition in a lipid bilayer. II. Influence of adamantane derivatives.

The influence of thirty-four adamantane, protoadamantane, and homoadamantane derivatives on the phase transition characteristics of the bilayer in dipalmitoyl lecithin liposomes has been determined by differential scanning calorimetry. Each of these compounds induces a broadening of the phase transition profile of the lipid bilayer that is dependent upon the concentration of the solute and its molecular structure. The concentration--response curves obtained for these solutes suggest that the cage compound derivatives modify the phase properties and under some conditions may induce a phase separation in the doped bilayer. The relative activity sequences obtained for the compounds examined cannot be accounted for by simple considerations of lipid/water partition coefficients, substitution constants based on free energy relationships, or the relative polarities or sizes of substituent groups. The observations are consistent with the hypothesis that the position and orientation of a solute within the bilayer are critical factors in determining its relative potency. The position of a solute within the bilayer is significantly controlled by the presence of polar substituents and by the relative geometric relationships of these groups. For a given substituent group, the shape and size of the hydrocarbon cage becomes increasingly important. It is apparent that seemingly minor modifications in the structure of a solute can significantly alter its influence on the phase transition behavior of a bilayer.

Studies on the glycolipids of human saliva and gastric juice.

It has been reported that both human saliva and gastric juice (cf. Slomiany, B. L., and Slomiany, A. (1980) in Cell Surface Glycolipids (Sweeley, C. C., ed) American Chemical Society Symposium, No. 128, pp. 149-176, American Chemical Society, Washington, D.C.) contain substantial amounts of certain members of a series of novel glucoglycerolipids with a 1-O-alkyl glyceryl ether backbone. We have analyzed the glycolipids present in samples of saliva obtained from 10 individuals and in samples of gastric juice obtained from 5 individuals. In both fluids, compounds corresponding in the properties studied to standards of glucosyl- and lactosylceramides were found to be the major glycolipids. Other more complex glycosphingolipids were also present in smaller amounts. Human saliva was found to contain two glucoglycerolipids that were not detected in gastric juice. Analyses of these compounds indicated that they were mono- and diglucosyl diglycerides and were probably of bacterial origin. Methanolysis of the glycolipid fractions of saliva and gastric juice failed to reveal the presence of any more than traces of 1-O-alkyl glyceryl ethers. Our results do not exclude the possibility that glyceryl ether-containing glucoglycerolipids occur in human saliva and gastric juice. However, at most they would appear to be rather minor components of either fluid.